Can Oxygen Tension Contribute to an Abnormal Placental Cytokine Milieu?

Abstract

OBJECTIVE The aim of this study was to determine whether culturing human placental explants under different oxygen tensions will alter expression of pro- and anti-inflammatory mediators. METHODS Placental explant cultures from second-trimester, elective, terminations-of-pregnancy were incubated under 21, 5, or 1% O(2) concentrations for 24 hr in the presence or absence of IL-10. Cytokine concentrations in the conditioned medium were quantified by immunoassay. RESULTS Culture of placental explants under 21, 5, or 1% O(2) concentrations produced hyperoxic (143 ± 1.6 mmHg), normoxic (37 ± 1.6 mmHg), and hypoxic (18.2 ± 1.6 mmHg) pO(2) levels for the maternal-fetal interface in the medium. Oxygen tension had profound effects on basal placental cytokine levels as well as on IL-10-stimulated cytokine production. IL-1β and TNF-α, but not IFN-γ production, was reduced by 21% O(2) . Moreover, 21% O(2) levels increased the anti-inflammatory cytokines IL-10 and IL-13 while 1% O(2) tended to decrease the production of these cytokines. CONCLUSIONS Five percent- O(2) incubation more accurately represents in vivo pO(2) conditions at the maternal-fetal interface. Routine culture of placental explants in room air produces a superphysiologic oxygen tension that tended to increase the production of anti-inflammatory and decrease the production of pro-inflammatory cytokines. In addition, low pO(2) may reduce responsiveness of the placenta to the anti-inflammatory actions of IL-10.